Evaluation of bioabsorbable calcium sulfate hemihydrate beads for local delivery of carboplatin

Abstract

The objectives of this study were to evaluate a novel kit of resorbable calcium sulfate beads marketed specifically for use in veterinary medicine and generally used for local delivery of antimicrobials as carboplatin-delivery system. The study characterized the elution of carboplatin in vitro, and investigated whether the initial dose and formulation of carboplatin, or the bead size significantly influences carboplatin elution in vitro. Calcium sulfate hemihydrate beads of 3- and 5-mm diameter were prepared. Five doses and two formulations of carboplatin (20, 50, 100, and 500 mg carboplatin per kit in powder formulation; 20 mg in liquid formulation) were tested in triplicates for each diameter beads. Beads were placed in 37°C phosphate buffered saline for 72 hours. Carboplatin concentrations in the eluent were measured by high-performance liquid chromatography at 11 time points with a modified United States Pharmacopeia assay. Concentrations of carboplatin in the eluent proportionally increased with the initial dose and peaked between 13 and 52 hours, ranging from 42.1% to 79.3% of the incorporated load. Higher peak concentrations, percentages released, and elution rates were observed with the liquid formulation and with higher carboplatin doses. There was no significant difference in maximum carboplatin concentrations between 3-and 5-mm diameter beads, but 5-mm diameter beads had slower elution rates. The novel kit can be used for preparation of carboplatin-impregnated resorbable calcium sulfate beads at variable doses, sizes and formulations. Further study is warranted to define the in vivo requirements and effective carboplatin dose, spatial diffusion and desired duration of elution.